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European Training Network for Cell-based Regenerative Medicine

Periodic Reporting for period 2 - Training4CRM (European Training Network for Cell-based Regenerative Medicine)

Reporting period: 2018-11-01 to 2020-10-31

Training4CRM is addressing existing gaps within Cell-based Regenerative Medicine (CRM) for treatment of neurological diseases such as Parkinson´s, Huntington´s, and Epilepsy, which occur as a result of progressive loss of structure, function and/or death of neurons in the brain. These disorders have a high prevalence and are associated with short- and long-term impairments and disabilities with high emotional, financial and social burden to the patients, their families and their social network.
An inter- and transdisciplinary educational program was established for early-stage researchers (ESRs) from different scientific disciplines to equip them with both scientific- and transferable skills, accustoming them to stepping out of their own comfort zones and work together on new ideas and problems, with the ambition to reach new horizons in CRM together. The Training4CRM project vision is shown in Fig 1.

To meet the gap within CRM for the mentioned neurological disorders, the overall objective was to recruit, educate and train 15 ESRs in a specially designed Training for CRM program in which the ESRs should become accomplished within and across different scientific disciplines, mastering the design, fabrication and testing of completely new tools and materials relevant to CRM within the fields of micro-and nanoengineering, biotechnology and pre-clinincal studies. At the end of the program the ultimate goal was to develop the ESRs into highly inter-disciplinary researchers with transferrable skills, capable of mastering techniques and methods across the borders of their own disciplines, recognizing ideas applicable to their own work, as well as being able to communicate and exploit their research and findings to the benefit for society as a whole. Fig 2 shows all 15 ESRs and how their projects are interlinked with the overall vision of the Training4CRM project.
Training4CRM successfully recruited 15 ESRs, who all were trained and active in different scientific disciplines, transferrable skills, and communication and exploitation through dedicated and custom designed Training4CRM research schools (RS), outreach activities and video production, organisation (fully by the ESRs) an international neuroscience conference (finally on-line) in the midst and in spite of the Covid-19 lock-down, as well as participation in business plan contests and start-up activities. Through collaborative and cross-disciplinary efforts of the ESRs, their research has led to highly innovative state of the art results and publications and have in common achieved most of the Training4CRM objectives.

Training4CRM has been an exciting, challenging and pleasurable experience for all participants with many new ideas, partnerships and friendships as a result (Fig 3).
The Training4CRM program has been centred around 3 scientific & technological workpackages, WP1-3, each with dedicated ESRs linked to them. However, ESRs have contributed and collaborated across WPs throughout the project duration. WP4 involved project management and WP5 training and education of ESRs in cross-disciplinary scientific topics related to the project as well as various transferrable skills. WP6 involved the project´s communication and exploitation strategies closely linked to the training program in WP5. WP7 and WP8 involved issues relating to Ethics.

All 15 ESRs have participated in the four research school (RS), specifically designed by the different beneficiaries to meet the ESR needs: RS1-Micro and Nanoengineering, RS2-Biotechnology, RS3-Pre-clinical analysis, and RS4-Exploitation of knowledge.

The ESRs have arranged a range of dissemination and outreach activities:
(1) Designed and updated the Training4CRM website, they produced the project logos and templates, and started Training4CRM social accounts.
(2) Organised two major public outreach events (Fig 4) and produced a video explaining the project (https://youtu.be/vF-aeKE34dE).
(3) Took part in business plan competitions, won prizes and raised money for Legendary Vish (https://www.legendaryvish.com) a start-up for 3D printed plant-based seafood.
(4) Organised a conference “Advanced Therapies in Neurodegeneration Bridging Neuroscience, Bioengineering and Optogenetics” https://www.mariecuriealumni.eu/events/advanced-therapies-neurodegeneration-bridging-neuroscience-bioengineering-and-optogenetics). It was originally planned for April 2020 in Lisbon Portugal, but due Covid-19 outbreak, reorganised to be online.

Their research has led to:
(1) Genetically modified human stem cells capable of delivering therapeutic factors to protect neurons during transplantation, and optogenetically modified cells that when light stimulated trigger the release of neurotransmitters, as well as their preclinical testing for CRM in animal models.
(2) Decellularized extra cellular matrix to generate stem cell derived cerebral organoids, and in combination with 3D printed scaffolds enhanced flat brain organoids, resulting in enhanced diffusion and gyrification.
(3) Different nano/microstructures that serve as substrates for culturing and differentiation of stem cells, as drug delivery systems for light triggered drug release, as optical waveguides for light stimulation, and electrodes for electrical/electrochemical sensing/stimulation.
(4) Electronic instrumentation and devices to model neurodegenerative disorders, miniaturised optoelectrical and electronic probes as potential novel and future wireless controlled neural implants for CRM.
(5) The Felix BIOprinter (https://www.felixprinters.com/felix-bioprinter) has been developed in Training4CRM by FelixRobotics in collaboration with DTU, now manufactured and sold by FelixPrinters.

Training4CRM has so far resulted in 17 published or accepted papers, a number of submitted manuscripts with more manuscripts in the pipeline.
The number of PD patients is predicted to double by 2030 due to the ageing population, and neurogenerative diseases, such as Epilepsy and PD, are estimated to surpass cancer as the most common group of medical conditions by 2040. Moreover, the annual European cost of PD and Epilepsy is estimated at approx. 27 billion Euro, with a clearly rising trend. To deal with this societal-wide burden, challenge-driven multidisciplinary research and innovation is needed to develop intelligent optogenetic DBS implants for neurodegenerative diseases.

The formalised inter-disciplinary training and the wide set of transferrable skills, potentiates the ESRs employability. By moving between the complementary research groups in Training4CRM, the ESRs have transferred cutting-edge knowledge from leading universities into relevant companies and brought new business and research perspectives from industry to academia and vice versa (e.g. The new Felix Bioprinter and the start-up Legendary Vish).
The ESRs has received an integrated academic/commercial program far beyond what would be possible through work at any single institution or an exclusively academic doctoral programme. The interdisciplinary and intercultural knowledge acquired within the research training program, the transferrable skills training, and the exposure to training in entrepreneurship by the industrial partners will generate highly employable researchers for jobs in academia and in industry research, development and production/commercialization in both established companies and small start-up companies.
Figure 4. Outreach event organised by ESRs in Barcelona 2019
Figure 3. Project dinner at research school 4 in Barcelona 2019
Figure 1. Training4CRM vision-Envisaged personalized brain bioimplant for CRM
Figure 2.ESRs and how their projects are interlinked with the Training4CRM vision